Abstract for IMM91021

Dose Range-Finding on the Immunological Evaluation of Carbon Tetrachloride in Female B6C3F1 Mice

Abstract

The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program. The findings have not been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by NTP in March 2009. The findings and conclusions for this study should not be construed to represent the views of the NTP or the U.S. Government.

Carbon tetrachloride was nominated to the NTP for toxicological evaluation and was selected for immunotoxicity studies by the chemical manager. Thus, the purpose of these range-finding studies was to determine the doses of carbon tetrachloride and the exposure period to be used in the protocol to determine the potential effects of carbon tetrachloride on the immune system.

The range-finding studies were conducted in female B6C3F1 mice. The animals were administered carbon tetrachloride daily for 7 days by oral gavage. Carbon tetrachloride was prepared as a solution in corn oil. In completing the range-finding protocol, two studies were conducted. In both studies, three dose levels, 100, 500 and 1000 mg/kg, of carbon tetrachloride were administered.

The results of the carbon tetrachloride range-finding studies demonstrate that, in the female B6C3F1 mouse, exposure to carbon tetrachloride, administered by oral gavage for 7 days at doses of 100, 500, or 1000 mg/kg, was not overly toxic in that all of the animals survived the exposure period. Carbon tetrachloride exposure did no affect body weight or body weight gain. Furthermore, there was no effect on hematological parameters or organ weights with the exception of the liver which increased in weight dose dependently. The 7-day exposure period did not result in an altered spleen IgM plaque-forming cell response to the T-dependent antigen, sheep erythrocytes. However, in the animals receiving the 500 and 1000 mg/kg dose levels of carbon tetrachloride, the mixed leukocyte response was decreased 35% and 29%, respectively. Based on the toxicological and immunological results of these range-finding studies, doses of 50, 100, and 500 mg/kg will be used in the carbon tetrachloride 14-day protocol study.